Barrier tissues are primary targets of environmental stressors and home to the largest number of antigen-experienced lymphocytes in the body, including commensal-specific T cells.
Here, we show that skin-resident commensal-specific T cells harbor a paradoxical program characterized by a type-17 program associated with a poised type-2 state.
Thus, in the context of injury and exposure to inflammatory mediators such as IL-18, these cells rapidly release type-2 cytokines, thereby acquiring contextual functions. Notably, such acquisition of a type-2 effector program promotes tissue repair.
Aberrant type-2 responses can also be unleashed in the context of local defects in immunoregulation. Thus, commensal-specific T cells co-opt tissue residency and cell-intrinsic flexibility as a means to promote both local immunity and tissue adaptation to injury.
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